This application is for support to purchase a single photon Zeiss 510 Meta laser confocal microscope. The instrument will be housed within the Bioimaging Facility of the Kimmel Cancer Center of Thomas Jefferson University. This Facility provides light microscopy services to users within the Kimmel Cancer Center, throughout Thomas Jefferson University, and as needed and available to investigators at neighboring research institutions. This instrument is critically needed to replace the existing Bio-Rad MRC-600 confocal microscope, which is over 11 years old, limited in its capabilities and increasingly problematic to maintain. Importantly, the requested instrument will provide new capabilities not currently available. These include the ability to image three distinct signals with precise registration and with high sensitivity, to conduct quantitative FRAP experiments on user-defined areas, to reliably reject signal bleed through, to carry out FRET experiments, and to provide the flexibility to resolve overlapping emission spectra. This application is submitted by a group of major users at Thomas Jefferson University within the Kimmel Cancer Center, in the Farber Institute of Neuroscience, and in the Department of Neurology, all of whom are well funded with multiple NIH-supported projects involving confocal microscopy, and extensive experience and need for confocal microscopy in their work. In addition, a group of new users includes investigators at earlier stages of career with particular need for confocal microscopy that cannot readily be addressed by the existing instrumentation, such as imaging of Zebrafish and immune synapse formation. Acquisition of the proposed instrument will allow these and other investigators to more effectively carry out their work, and to use and develop state-of-the-art techniques in confocal microscopy in their studies.